The objective of the proposed research is twofold. The first objective is to further the knowledge of the mechanisms that control the normal development of the inner ear. The second and interrelated objective of the research is to examine models of abnormal development of the inner ear. The pathological mechanisms of development found will be compared to the normal mechanisms of development studied. The research plan will utilize the techniques of organ culture of the inner ear and autoradiography with tritium labeled precursors of DNA, RNA and protein synthesis. The strains of mice will be the normal (CBA-J) and two deaf mutants (shaker-l and kreisler). The projects under investigation will be (1) transfilter interaction of normal and abnormal developing otocysts, rhombencephalon and mesenchyme tissues in vitro, (2) the effect of neural innervation upon differentiation of the embryonic inner ear in vitro, (3) fate mapping of embryonic mouse otocyst, (4) the synthesis of RNA, DNA and protein in the cells of the inner ears of normal mice and the shaker-l strain of mutant mice that exhibit progressive deafness, (5) the cell kinetics of neural tube and otic mesenchyme of eleven-day embryos of the homozygotic kreisler mouse.